Variant 10-46010437-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001145263.2(NCOA4):c.1484C>T(p.Ser495Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00227 in 1,614,176 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0023 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 23 hom. )

Consequence

NCOA4
NM_001145263.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.32

Variant links:

Genes affected

NCOA4 (HGNC:7671): (nuclear receptor coactivator 4) This gene encodes an androgen receptor coactivator. The encoded protein interacts with the androgen receptor in a ligand-dependent manner to enhance its transcriptional activity. Chromosomal translocations between this gene and the ret tyrosine kinase gene, also located on chromosome 10, have been associated with papillary thyroid carcinoma. Alternatively spliced transcript variants have been described. Pseudogenes are present on chromosomes 4, 5, 10, and 14. [provided by RefSeq, Feb 2009]

NCOA4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014239132).

BP6

Variant 10-46010437-G-A is Benign according to our data. Variant chr10-46010437-G-A is described in ClinVar as [Benign]. Clinvar id is 715257.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00226 (344/152298) while in subpopulation EAS AF= 0.0189 (98/5184). AF 95% confidence interval is 0.0159. There are 3 homozygotes in gnomad4. There are 166 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCOA4	NM_001145263.2 linkuse as main transcript	c.1484C>T	p.Ser495Leu	missense_variant	8/10	ENST00000581486.6	NP_001138735.1	Q13772-1A0A024QZI5B2R5V0Q96E88

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCOA4	ENST00000581486.6 linkuse as main transcript	c.1484C>T	p.Ser495Leu	missense_variant	8/10	1	NM_001145263.2	ENSP00000462943.1		Q13772-1

Frequencies

GnomAD3 genomes

AF:

0.00227

AC:

345

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00471

Gnomad ASJ

AF:

0.00662

Gnomad EAS

AF:

0.0191

Gnomad SAS

AF:

0.00827

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00125

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00451

AC:

1132

AN:

251246

Hom.:

AF XY:

0.00415

AC XY:

564

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.000309

Gnomad AMR exome

AF:

0.0115

Gnomad ASJ exome

AF:

0.00516

Gnomad EAS exome

AF:

0.0186

Gnomad SAS exome

AF:

0.00630

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00102

Gnomad OTH exome

AF:

0.00392

GnomAD4 exome

AF:

0.00227

AC:

3319

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00234

AC XY:

1705

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.0107

Gnomad4 ASJ exome

AF:

0.00551

Gnomad4 EAS exome

AF:

0.0134

Gnomad4 SAS exome

AF:

0.00639

Gnomad4 FIN exome

AF:

0.0000936

Gnomad4 NFE exome

AF:

0.00120

Gnomad4 OTH exome

AF:

0.00429

GnomAD4 genome

AF:

0.00226

AC:

344

AN:

152298

Hom.:

Cov.:

AF XY:

0.00223

AC XY:

166

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.000505

Gnomad4 AMR

AF:

0.00471

Gnomad4 ASJ

AF:

0.00662

Gnomad4 EAS

AF:

0.0189

Gnomad4 SAS

AF:

0.00828

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00125

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00163

Hom.:

Bravo

AF:

0.00286

Asia WGS

AF:

0.0210

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_noAF

Pathogenic

0.54

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.37

T;T;T;T;.;.;.

LIST_S2

Benign

0.82

.;T;T;.;T;T;T

MetaRNN

Benign

0.014

T;T;T;T;T;T;T

Sift4G

Uncertain

0.0030

D;D;D;D;D;D;D

Vest4

0.38

gMVP

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over